tetano
Editor, Senior Moderator
Clin Infect Dis
. 2025 Feb 17:ciaf029.
doi: 10.1093/cid/ciaf029. Online ahead of print. Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial
Anne F Luetkemeyer[SUP] 1 [/SUP], Kara W Chew[SUP] 2 [/SUP], Stuart Lacey[SUP] 3 [/SUP], Michael D Hughes[SUP] 4 [/SUP], Linda J Harrison[SUP] 4 [/SUP], Eric S Daar[SUP] 5 [/SUP], Joseph Eron[SUP] 6 [/SUP], Courtney V Fletcher[SUP] 7 [/SUP], Alexander L Greninger[SUP] 8 [/SUP], Diane Hessinger[SUP] 9 [/SUP], Jonathan Z Li[SUP] 10 [/SUP], David Mailhot[SUP] 9 [/SUP], David Wohl[SUP] 6 [/SUP], Methee Chayakulkeeree[SUP] 11 [/SUP], Jose Luis Accini Mendoza[SUP] 12 [/SUP], Polina Elistratova[SUP] 13 [/SUP], Oluwaseun Makinde[SUP] 13 [/SUP], Gareth Morgan[SUP] 14 [/SUP], Simon Portsmouth[SUP] 13 [/SUP], Takeki Uehara[SUP] 15 [/SUP], Davey Smith[SUP] 16 [/SUP], Judith S Currier[SUP] 2 [/SUP]
Affiliations
Background: Ensitrelvir, a severe acute respiratory syndrome coronavirus-2 main protease inhibitor, has demonstrated clinical and virologic efficacy in previous studies.
Methods: In this global phase 3 trial, nonhospitalized adults with mild-to-moderate coronavirus disease 2019 (COVID-19) and symptom onset within 5 days were randomized (1:1) to receive once-daily ensitrelvir (375 mg day 1, 125 mg days 2-5) or blinded matching placebo. The primary endpoint was the restricted mean time to sustained (≥2 days) resolution of 15 COVID-19 symptoms, recorded in participant daily diaries, through day 29 in participants starting treatment within 3 days after symptom onset. Virologic efficacy and safety were assessed.
Results: Of 2093 participants, 1888 started treatment within 3 days after symptom onset. Mean time to symptom resolution was 12.5 and 13.1 days with ensitrelvir and placebo, respectively (difference, -0.6 days; 95% confidence interval, -1.38 to 0.19; P = .14). On day 4, ensitrelvir reduced least-squares mean RNA by 0.72 log10 copies/mL more than placebo (95% confidence interval, 0.55-0.90). Among those with positive viral cultures at enrollment, 274/287 (95.5%) ensitrelvir-treated versus 210/280 (75.0%) placebo-treated participants had negative cultures on day 4. RNA rebound was similar (<1.5%) between groups. The proportion of participants with ≥1 adverse event was similar with ensitrelvir (61.5%) and placebo (60.6%). No treatment-related serious adverse events or deaths occurred. Three (0.3%) ensitrelvir-treated and 1 (0.1%) placebo-treated participants had COVID-19-related hospitalizations by day 29.
Conclusions: Despite the evidence of antiviral activity with ensitrelvir, this trial did not demonstrate a significant difference in time to sustained symptom resolution.
Keywords: COVID-19; ensitrelvir; high risk; symptom resolution; viral rebound.
. 2025 Feb 17:ciaf029.
doi: 10.1093/cid/ciaf029. Online ahead of print. Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial
Anne F Luetkemeyer[SUP] 1 [/SUP], Kara W Chew[SUP] 2 [/SUP], Stuart Lacey[SUP] 3 [/SUP], Michael D Hughes[SUP] 4 [/SUP], Linda J Harrison[SUP] 4 [/SUP], Eric S Daar[SUP] 5 [/SUP], Joseph Eron[SUP] 6 [/SUP], Courtney V Fletcher[SUP] 7 [/SUP], Alexander L Greninger[SUP] 8 [/SUP], Diane Hessinger[SUP] 9 [/SUP], Jonathan Z Li[SUP] 10 [/SUP], David Mailhot[SUP] 9 [/SUP], David Wohl[SUP] 6 [/SUP], Methee Chayakulkeeree[SUP] 11 [/SUP], Jose Luis Accini Mendoza[SUP] 12 [/SUP], Polina Elistratova[SUP] 13 [/SUP], Oluwaseun Makinde[SUP] 13 [/SUP], Gareth Morgan[SUP] 14 [/SUP], Simon Portsmouth[SUP] 13 [/SUP], Takeki Uehara[SUP] 15 [/SUP], Davey Smith[SUP] 16 [/SUP], Judith S Currier[SUP] 2 [/SUP]
Affiliations
- PMID: 39960062
- DOI: 10.1093/cid/ciaf029
Background: Ensitrelvir, a severe acute respiratory syndrome coronavirus-2 main protease inhibitor, has demonstrated clinical and virologic efficacy in previous studies.
Methods: In this global phase 3 trial, nonhospitalized adults with mild-to-moderate coronavirus disease 2019 (COVID-19) and symptom onset within 5 days were randomized (1:1) to receive once-daily ensitrelvir (375 mg day 1, 125 mg days 2-5) or blinded matching placebo. The primary endpoint was the restricted mean time to sustained (≥2 days) resolution of 15 COVID-19 symptoms, recorded in participant daily diaries, through day 29 in participants starting treatment within 3 days after symptom onset. Virologic efficacy and safety were assessed.
Results: Of 2093 participants, 1888 started treatment within 3 days after symptom onset. Mean time to symptom resolution was 12.5 and 13.1 days with ensitrelvir and placebo, respectively (difference, -0.6 days; 95% confidence interval, -1.38 to 0.19; P = .14). On day 4, ensitrelvir reduced least-squares mean RNA by 0.72 log10 copies/mL more than placebo (95% confidence interval, 0.55-0.90). Among those with positive viral cultures at enrollment, 274/287 (95.5%) ensitrelvir-treated versus 210/280 (75.0%) placebo-treated participants had negative cultures on day 4. RNA rebound was similar (<1.5%) between groups. The proportion of participants with ≥1 adverse event was similar with ensitrelvir (61.5%) and placebo (60.6%). No treatment-related serious adverse events or deaths occurred. Three (0.3%) ensitrelvir-treated and 1 (0.1%) placebo-treated participants had COVID-19-related hospitalizations by day 29.
Conclusions: Despite the evidence of antiviral activity with ensitrelvir, this trial did not demonstrate a significant difference in time to sustained symptom resolution.
Keywords: COVID-19; ensitrelvir; high risk; symptom resolution; viral rebound.